Device and method of particle focusing

ABSTRACT

A method of focusing a plurality of discrete particles. The method comprises establishing a flow of a fluid medium carrying a plurality of discrete particles within a capillary having a plurality of separate walls and a longitudinal axis. The method further includes vibrating the plurality of separate walls to apply an acoustic field having a central axis substantially along the longitudinal axis to focus the plurality of discrete particles substantially along the longitudinal axis.

RELATED APPLICATIONS

This application claims the benefit of priority of U.S. ProvisionalPatent Application No. 61/149,061, filed on Feb. 2, 2009, the contentsof which are incorporated by reference as if fully set forth herein.

FIELD AND BACKGROUND OF THE INVENTION

The present invention, in some embodiments thereof, relates to aparticle focusing and, more particularly, but not exclusively, tomethods and systems of acoustic focusing.

Aerodynamic focusing is a mechanism that has been widely used to produceparticle beams, for example tightly collimated particle beams. Using theaerodynamic lenses, near-axis particles can be focused onto a streamlinein principle. An aerodynamic lens system typically consists of threeparts: a flow control orifice, focusing lenses, and an accelerationnozzle. The choked inlet orifice fixes the mass flow rate through thesystem and reduces pressure from ambient to the value required toachieve aerodynamic focusing. The focusing lenses are a series oforifices contained in a tube that create converging-diverging flowaccelerations and decelerations, through which particles are separatedfrom the carrier gas due to their inertia and focused into a tightparticle beam. The accelerating nozzle controls the operating pressurewithin the lens assembly and accelerates particles to downstreamdestinations. Aerodynamic lenses have been widely used in particle massspectrometers. Available designs for aerodynamic lenses effectivelycollimate particles as small as 30 nm.

At present, focusing of a range of micron and submicron size aerosolparticles is carried out using aerodynamic forces in periodicaerodynamic lens arrays, see Liu, P., Ziemann, P. J., Kittelson, D. B.and McMurry, P. H. (1995) Aerosol Sci. Techn., 22, 293-3 13 and Wang,X., Gidwani, A., Girshick, S. L. and McMurry, P. H. (2005). Aerosol Sci.Techn., 39, 624-636., which are incorporated herein by reference. Sucharrays are used as inlets to on-line single-particle analyzers; seeWexler, A. S. and Johnston, M. V. (2001) in Aerosol Measurement:Principles, Techniques, and Applications. P. A. Baron and K. Willekeed., Wiley, New York, which is incorporated herein by reference.

Hydrodynamic focusing is a technique usually used to provide resultsfrom flow cytometers or Coulter counters for determining the size ofbacteria or cells. When using Hydrodynamic focusing for flow cytometrymicroscopic particles, such as cells and chromosomes, are counted andexamined by suspending them in a stream of fluid and passing them by anelectronic detection apparatus.

Acoustic focusing, such as Acoustic cytometry, is a technology that isused for focusing cells or particles with acoustic radiation pressureforces. For example acoustic focusing is employed in flow cytometryanalysis, either as a substitute for hydrodynamic focusing or incombination with it, is described in Curr. Protoc. Cytom.49:1.22.1-1.22.12. © 2009 by John Wiley & Sons, Inc, which isincorporated herein by reference. The use of acoustic standing waves toconcentrate initially homogeneously suspended aerosol or hydrosolparticles in acoustic pressure nodal or antinodal planes was firstvisualized by Kundt (1866) and then described by and Rayleigh (1945).Subsequent works utilize this phenomenon (see Duhin, 1960; Czyz, H.,1990; Damn et al., 1995; Vainshtein et al., 1996 and papers citedtherein) for various applications. The acoustic force was also used toposition and levitate particles (see King, 1934; Fuchs, 1964; Coakley etal., 1989; Gopinath and Mills, 1994; Hertz, 1995 and papers citedtherein). In those works the particle motion was studied in situationswhen undisturbed fluid was at rest. A number of devices and method havebeen used to use acoustic waves to concentrate aerosol or hydrosolparticles. An example of using acoustic focusing technology is describedin U.S Patent Application Publication number 2010/0009333, filed on 17Jun. 2009 that describes methods for using acoustic focusing technologyon its own or in conjunction with hydrodynamic focusing for analyzingbiological samples. In one application, a preferential orientation ofbiological particles is achieved by applying a substantially ellipticalacoustic field. The application describes a sample comprising a fluidmedium carrying a plurality of discrete biological particles which arepre-concentrated in-line with a sample analyzer, such as a flowcytometer, where a sheath fluid is introduced after acousticpre-concentration. The application describes methods for acousticallyseparating suspended discrete biological particles of differentdensities from a fluid medium.

SUMMARY OF THE INVENTION

According to some embodiments of the present invention there is provideda method of focusing a plurality of discrete particles. The methodcomprises establishing a flow of a fluid medium carrying a plurality ofdiscrete particles within a capillary having a plurality of separatewalls and a longitudinal axis and vibrating the plurality of separatewalls to apply an acoustic field having a central axis substantiallyalong the longitudinal axis, the acoustic field focusing the pluralityof discrete particles substantially along the longitudinal axis.

Optionally, the plurality of separate walls are separately vibrated in afrequency of less than 10 Mega Hertz (10 MHZ).

Optionally, the acoustic field is a substantially quadrupole acousticfield.

Optionally, the method comprises analyzing signals received from theparticles, substantially along the longitudinal axis, to identify atleast one characteristic of the plurality of discrete particles.

Optionally, the acoustic field creates a plurality of streamlines eachbetween two adjacent walls of the plurality of separate walls; theapplying comprises maneuvering the plurality of particles along thestreamlines, toward the longitudinal axis.

Optionally, the vibrating comprises maneuvering each the particle inoscillating motions toward the longitudinal axis.

Optionally, the plurality of particles are plurality of discreteparticles.

Optionally, the plurality of separate walls form a substantiallyunpartitioned inner lumen.

Optionally, the vibrating comprising vibrating plurality of separatewalls are separately vibrated in a frequency of about 1 Kilo Hertz (1KHz).

According to some embodiments of the present invention there is provideda device of focusing a plurality of particles. The device comprises acapillary having a longitudinal axis and a substantially unpartitionedlumen to flow a fluid medium having a plurality of particles and atleast one vibration source for vibrating the capillary in a frequency ofless than 10 Mega Hertz (MHz) so as to focus the plurality of particlesalong the longitudinal axis.

Optionally, the inner lumen having a diameter of about 10 millimeter.

Optionally, the capillary having a plurality of separate walls and aplurality of slits, each the slit being formed between each adjacentpair of walls of the plurality of separate walls.

More optionally, the plurality of separate walls are separated from oneanother.

More optionally, each the vibration source is connected to vibrate oneof the plurality of separate walls.

More optionally, each separate wall is convex toward a longitudinal axisof the capillary.

More optionally, each separate wall is concave toward a longitudinalaxis of the capillary.

More optionally, the at least one vibration source comprises a pluralityof vibration sources arranged to vibrate the capillary so as to form aquadrupole acoustic field having a central axis substantially along alongitudinal axis of the capillary.

Optionally, the capillary having four plurality of separate wallsarranged to form a cylindrical lumen.

An aerodynamic lens array having the aforementioned device as a lens inat least one stage.

A single-particle analyzer having the aforementioned device for focusingthe plurality of particles before an analysis thereof.

According to some embodiments of the present invention there is provideda device of focusing a plurality of particles. The device comprises acapillary having a longitudinal axis and a plurality of walls sized andshaped to flow a fluid medium having a plurality of particles and aplurality of vibration sources each separately vibrates one of theplurality of walls so as to focus the plurality of particles along thelongitudinal axis.

Unless otherwise defined, all technical and/or scientific terms usedherein have the same meaning as commonly understood by one of ordinaryskill in the art to which the invention pertains. Although methods andmaterials similar or equivalent to those described herein can be used inthe practice or testing of embodiments of the invention, exemplarymethods and/or materials are described below. In case of conflict, thepatent specification, including definitions, will control. In addition,the materials, methods, and examples are illustrative only and are notintended to be necessarily limiting.

BRIEF DESCRIPTION OF THE DRAWINGS

Some embodiments of the invention are herein described, by way ofexample only, with reference to the accompanying drawings. With specificreference now to the drawings in detail, it is stressed that theparticulars shown are by way of example and for purposes of illustrativediscussion of embodiments of the invention. In this regard, thedescription taken with the drawings makes apparent to those skilled inthe art how embodiments of the invention may be practiced.

In the drawings:

FIG. 1 is a schematic illustration of an exemplary capillary having forseparate walls, convex toward the longitudinal axis of said exemplarycapillary, according to some embodiments of the present invention;

FIG. 2 is a schematic illustration of another exemplary capillary havingfor separate walls, concave toward the longitudinal axis of saidexemplary capillary, according to some embodiments of the presentinvention;

FIG. 3 is a cross sectional schematic illustration of an exemplarycapillary having temping drills of vibration sources, according to someembodiments of the present invention;

FIG. 4 is flowchart of focusing a plurality of discrete particles,according to some embodiments of the present invention;

FIG. 5 is a cross sectional schematic illustration of a fluidstreamlines in a capillary, where the arrows depict the directions ofthe fluid oscillations of the fluid streamlines, according to someembodiments of the present invention;

FIGS. 6A and 6B are schematic illustrations of particles' trajectoriesstarting in an upstream region at various spatial locations along thelongitudinal axis of the capillary and dynamically concentrating in anarrower region, according to some embodiments of the present invention;and

FIG. 7 is a schematic illustration of trajectories of two particles in acapillary, such as depicted in FIG. 1, when an acoustic field is appliedthereon, according to some embodiments of the present invention.

DESCRIPTION OF EMBODIMENTS OF THE INVENTION

The present invention, in some embodiments thereof, relates to aparticle focusing and, more particularly, but not exclusively, tomethods and systems of acoustic focusing.

According to some embodiments of the present invention there is providedmethod and device of focusing a plurality of discrete particles in afluid flow capillary. The method is based on establishing a flow of afluid medium carrying a plurality of discrete particles within acapillary having a plurality of walls, for example 4 walls, optionallyseparated from one another. The focusing is performed by vibrating thewalls, optionally separately, to apply an acoustic field having acentral axis substantially along the longitudinal axis of the capillary.The acoustic field focuses the discrete particles substantially alongthe longitudinal axis. Optionally, the capillary is sized and shaped toapply the acoustic field by wall vibrations in a frequency of less than10 Mega Hertz (MHz), for example less than 1 MHz, less than 20 KHz, suchas about 1 KHz. In such a manner, sensitive particles, such as cells andbacteria, may be concentrated without damage, or without a substantialdamage. Optionally, the acoustic field is a quadrupole acoustic fieldhaving a central axis substantially along the longitudinal axis of thecapillary. Optionally, the walls of the capillary are concave and/orconvex toward the longitudinal axis.

According to some embodiments of the present invention, there isprovided a device of focusing a plurality of particles. The devicecomprises a capillary having a substantially unpartitioned lumen and oneor more vibration sources for vibrating the capillary in a frequency ofless than 10 MHz, for example less than 1 MHz, so as to focus theplurality of particles by creating an acoustic field.

According to some embodiments of the present invention there is provideda device of focusing particles having a capillary with a plurality ofseparate walls which are sized and shaped to flow a fluid medium havingthe particles. The device further includes a plurality of vibrationsources which are designed to vibrate separately each one of theseparate walls so as to focus the plurality of particles by creating anacoustic field, optionally substantially quadrupole.

Before explaining at least one embodiment of the invention in detail, itis to be understood that the invention is not necessarily limited in itsapplication to the details of construction and the arrangement of thecomponents and/or methods set forth in the following description and/orillustrated in the drawings and/or the Examples. The invention iscapable of other embodiments or of being practiced or carried out invarious ways.

Reference is now made to FIG. 1 which is a schematic illustration of adevice 100 of focusing a plurality of discrete aerosol and/or hydrosolparticles by an acoustic field, according to some embodiments of thepresent invention. The device 100 includes a capillary 102 forconducting flowing fluid, such as liquid or gas, optionally by a pumpthat is connected thereto. As used herein, a capillary means a channelor chamber having a cylindrical or quasi cylindrical shape having a baseselected from rectangular, square, elliptical, oblate circular, round,octagonal, heptagonal, hexagonal, pentagonal, and/or triangular. Theshape of the interior walls of the capillary 102 may or may not be thesame as the shape of the exterior walls.

The capillary 102 is optionally an unpartitioned capillary 102 that isnot divided to chambers. In such a manner, particles which flow in thecapillary 102 can easily be washed out from the capillary 102. In suchan unpartitioned capillary, contaminations are avoided or reduced asparticles are not accumulated in around edges of the partitions. Thus,an analysis of a beam of particles generated by the device 100 is moreaccurate and/or stable than the analysis of a beam of particlesgenerated by a similar device with a plurality of chambers in its innerlumen.

According to some embodiments of the present invention, as shown at FIG.1, the capillary 102 has a plurality of separate walls 104, optionally4. A slit is formed in parallel, or substantially in parallel, to thelongitudinal axis 105 of the capillary 102, between each adjacent pairof the walls, as shown at 103.

Optionally, each separate wall is convex toward the longitudinal axis105, as shown at FIG. 1. Optionally, each separate wall is concavetoward the longitudinal axis 105, as shown at FIG. 2.

One or more vibration sources for vibrating the unpartitioned capillaryare connected to the separate walls 104. Optionally, as furtherdescribed below, the vibrating is performed in a frequency of less than10 Mega Hertz (MHz), for example less than 1 MHz, less than 20 KiloHertz (KHz), for instance about 1 KHz. Each vibration source may be atransducer. It should be noted that vibrating the capillary 102 with lowfrequency sound waves, such as about 1 KHz causes low attenuation.

Optionally, the diameter of the inner lumen 107 of the capillary isabout 10 millimeter (mm). In Goddard, G. and Kaduchak, G. (2005) J.Acoust. Soc. Am., 117 (6), 3440-3447 and Goddard, G., Martin, J. C.,Graves, S. W (hereinafter: “Goddard et al.”), and Kaduchak, G. (2006)Cytometry A, 69, 66-74, which are incorporated herein by reference,particles have been focused acoustically in a liquid flow in a capillaryhaving an inner lumen 108 of 10 mm 107. The device 100 allows focusingparticles in a gas flow and/or a liquid flow streamed in a capillaryhaving an inner lumen 108 of 10 millimeter (mm) 107. The particles areconcentrated in a beam substantially along the longitudinal axis 105. Insuch an embodiment, the device 100 is used as aerodynamic lens arrayshaving a size in the order of 10 mm. It should be noted that the highfrequency of ultrasound waves which are applied in used by Goddard etal. are not applicable to particle focusing of particles in a gas flowas it induces strong sound attenuation, see Krasilnikov, V. A. andKrylov, V. V. (1984) Introduction to Physical Acoustics, Nauka (inRussian), which is incorporated herein by reference.

Optionally, the device 100 has a separate vibration source forseparately vibrating each wall 104. Reference is now also made to FIG.3, which is a cross sectional schematic illustration of an exemplarycapillary, such as the exemplary capillary 102 depicted in FIG. 1,having temping drills of vibration sources 301, according to someembodiments of the present invention. FIG. 3 depicts exemplary locationsof the temping drills 301. Optionally, substrates are used to attach thedrills 301 to the walls 104. Optionally, flexible flanges are used tofacilitate the vibrations of the walls 104.

In the embodiment depicted in FIG. 3, magnetostrictive transducers 301are used to produce an acoustic field in the capillary 102. Eachtransducer consists of a number of magnetostrictive plates which arearranged in parallel to one another. Each transducer 301 is attached tothe bottom of the surface of one of the walls 104. For example, themagnetostrictive transducers 301 are ETREMA standard actuator made byETREMA Products, Inc., which are mounted to vibrate each of the walls104, for example model 200 of ETREMA Products, Inc. These actuatorsvibrate the walls with a frequency of about 1 KHz with a stroke of about±100 μm. Though these actuators are fairly large, about 35 cm long, itstamping drill is of 8.5 mm with pitch of 1 mm and optical density (OD)of 9.53 mm. In such a manner, they fit well to the size of the walls 104and can be easily attached to vibrate each one of the walls 104, forexample as shown at FIG. 3. Optionally, a pair of the walls 104, whichare opposite to one another, contract and expand suspension-filledchannel interior in phase and a pair of the walls 104, which areadjacent to one another, act in a counter-phase. In such a manner, aquadrupole excitation of fluid oscillations inside the capillary 102 isaccomplished. As outlined above and described below, the vibration ofthe walls 104 focuses particles, such as initially diluted aerosoland/or hydrosol particles, in a fluid medium that is delivered into thecapillary 102 for example by a pump connected thereto.

As further described below, this arrangement of vibration sources allowsforming a quadrupole acoustic field having a central axis substantiallyalong the longitudinal axis 105 of the capillary 105. For clarity, theuse of acoustic waves to concentrate initially homogeneously suspendedaerosol or hydrosol particles in acoustic pressure nodal or antinodalplanes is visualized in Kundt, A. (1866) Ann. Phys. and Chem. 127, 4,497 and then described in Rayleigh, Lord (1945) Theory of Sound, Vols 1an 2, 2nd Edn. Dover, which are incorporated herein by reference. Theutilization of this phenomenon is described in Damn, Y., Fichman, M.,Gutfinger, C., Pnueli D., Vainshtein, P., J. (1995) Aerosol Sci., 26,575, Duhin, S. S. (1960) Colloid J., 22, 128 (In Russian), Czyz, H.(1990) Acustica 70, 23, and Vainshtein, P., Fichman, Wl., Shuster, K.and Gutfinger, C. (1996) J. Fluid Mech., 306, 3 1-42 and in thereferences which are cited therein, all incorporated herein byreference. The acoustic force is used to position and levitateparticles, see King, L. V. (1934) Proc. Roy. Soc., 147A, 212-240, Fuchs,N. A. (1964) The Mechanics of Aerosols, Pergamon, Oxford, Coakley, W.T., Bardsley, D. W., Grundy, M. A., Zamani, F. and Clarke, D. J. (1989)J, Chem. Tech. Biotech. 44, 43, Gopinath, A. and Mills, A. F. (1994)Trans. ASME C: J. Heat Transfer, 1 16, 47-53, Hertz, H. M. (1995) J.Appl. Physics, 78, 4845-4849, and papers cited therein, all incorporatedherein by reference.

Reference is now also made to FIG. 4, which is a flowchart of a methodof focusing a plurality of discrete particles by applying an acousticfield, optionally quadrupole, according to some embodiments of thepresent invention.

First, as shown at 401, device having a capillary with a longitudinalaxis, such as shown at FIG. 1, is provided. Optionally, the capillary isstraight, or substantially straight.

Then, as shown at 402, a flow of a fluid medium is established withinthe capillary. The fluid medium carries a plurality of discrete hydrosolor aerosol particles. It should be noted that as the vibrations may beat low frequency of less than 20 Khz, for example 1 Khz, relativelysensitive particles, such as cells and Bactria may be concentrated.

Optionally, an axial gas flow is imposed in the x-direction, as shown at105 of FIG. 1. In such an embodiment, the fluid medium is agas-suspension flow in a capillary having an inner lumen 107 with adiameter of 2r₀=10 mm. In such an embodiment, the diameter of thecapillary 102 is equal to the distance between orifices in lens arrays,see Wang, X., Gidwani, A., Girshick, S. L. and McMurry, P. H. (2005).Aerosol Sci. Techn., 39, 624-636, which is incorporated herein byreference.

Now, as shown at 403, an acoustic field, optionally substantiallyquadrupole, having a central axis substantially along the longitudinalaxis is applied so as to focus the discrete hydrosol and/or aerosolparticles, optionally as a beam, along the longitudinal axis 105. Thegenerated field is applied to focus aerosol and/or hydrosol particleshaving a diameter that ranges between about few microns and about asubmicron size along the longitudinal axis 105.

The acoustic field is optionally applied by vibrating the capillary, forexample as described above. Optionally, the frequency of vibration,denoted herein as f, is about 1 kHz. For such a frequency, thewavelength, denoted herein as λ, in air is 34.4 cm.

Optionally, the diameter of the capillary 102, r₀, and the frequency ofthe vibration are set so as λ>>2r₀. In such a manner, no standing waveis formed inside the inner lumen 107, see, for example, Vainshtein, P.B., Fichman, M., Pnueli, D. (1992) J. Aerosol Science, 23 (6), 631-657,which is incorporated herein by reference. The pressure disturbances,which are induced by the vibrating of the walls 104, generatecross-sectional acoustic waves at the channel walls 104. These pressuredisturbances may be defined as follows

p−p ₀ =p _(s) cos ωt at y ² −z ² =r ₀ ²  (2); and

p−p ₀ =p _(s) cos ωt at z ² −y ² =r ₀ ²  (1)

where p_(s) denotes an amplitude of pressure oscillations, p₀ denotesundisturbed pressure, and ω=2πf. Solution of the Laplace equation,satisfying the boundary conditions on the walls 104, describes thepressure distribution in the capillary cross-sections, such that thecross-sectional pressure gradient is time-varying and proportional tothe distance from the longitudinal axis 105. As a result, thecross-sectional velocity field, obtained from the Navier-Stokesequations, is time-varying and vanishing at the channel axis (y=z=0).The cross-sectional velocity field may be defined as follows:

$\begin{matrix}{{v = {{- v_{s}}\frac{y}{r_{0}}\sin \; \omega \; t}},{w = {v_{s}\frac{z}{r_{0}}\sin \; \omega \; t}}} & {{Equation}\mspace{14mu} 1}\end{matrix}$

where v and w denotes cross-sectional components of the fluid velocityvector, u=(u, v, w), and

$\begin{matrix}{{Equation}\mspace{14mu} 2} & \; \\{v_{s} = {2\frac{p_{s}}{\rho_{f}\omega \; r_{0}}}} & (2)\end{matrix}$

where ρ_(f) denotes the fluid density and V_(s) denotes thecharacteristic amplitude of fluid velocity oscillations occurring in thechannel, and r₀ denotes the diameter of the inner lumen of thecapillary. For r₀, this amplitude is determined by the parameters of asound field, namely by the frequency and amplitude of wall oscillations.

The fluid velocity V, which is defined in Equation 1, is independent ofviscosity; however it satisfies the equations of the viscous flow andslip boundary condition. The latter is induced as the cross-sectionalvelocity vector is a normal to the channel walls 104, for example asdepicted in FIG. 5, which depicts a cross sectional schematicillustration depicting fluid streamlines where the arrows show thedirections of the fluid oscillations.

According to Equation 1, the fluid velocity oscillates along thestreamlines depicted in FIG. 5. It is linearly distributed and vanishingat the longitudinal axis 105. This leads a particles drift which movestowards the longitudinal axis 105 and focuses in a beam therealong.

Reference is now made to the focusing effect. Optionally, the flow is adiluted aerosol so that particle-particle interactions are negligibleand the presence of particles does not affect the carrier gas flowfield. In this explanation, the trajectories of a rigid, non-diffusiveparticle of radius a in the flow field defined in Equation 1. Thefluid-particle interaction may be described by a linear drag force, forexample as follows:

$\begin{matrix}{{\frac{u_{p}}{t} = \frac{u - u_{p}}{\tau}},{\tau = {2\; {a^{2}/9}\; v\; \Pi_{\rho}}}} & {{Equation}\mspace{14mu} 3}\end{matrix}$

where u_(p) denotes a particle velocity vector, τ denotes a Stokesrelaxation time, Π_(ρ) denotes a fluid-to particle-density ratio, and νdenotes a fluid kinematic viscosity. Such an approximation is valid foraerosol applications when Π_(ρ)ωτ<<1.

According to Equations 1-3, particles introduced into the capillary 102move due to the differences between their velocity and the fluidmedium's velocity. As a result, of the particles' trajectories startingin an upstream region at various spatial locations along thelongitudinal axis 105, are dynamically concentrated to the narrowerregion, as shown at FIGS. 6A and 6B. This concentrating effectassociated with particle inertia will lead to increase in particleconcentration by several orders of magnitude.

Each particle travels in oscillating motions as the fluid velocityoscillates. However, the particle is not entrained fully in theoscillating fluid flow owing to its inertia. It deviates from the fluidstreamlines, for example those shown at FIG. 5, and moves towards thelongitudinal axis, optionally in converging swing motions, as shown inFIGS. 6A and 6B which respectively depict a cross-sectional schematicillustration of the capillary 102 and a trajectory of a single particletherein and a calculation of the particle cross-sectional trajectorywhere a particle starts from coordinates y₀=z₀=0.15 drifts towardcoordinates x=y=0, deviating from the fluid streamlines sketched inFIGS. 5 and 6B, z and y are normalized by r₀. This occurs as the fluidcross-sectional velocity decreases toward the longitudinal axis 105. Theparticles remain in the longitudinal axis 105 as a particle movingtoward the longitudinal axis is applied with a larger hydrodynamic forceand passes a larger distance than a particle moving at the oppositedirection. Within every oscillating period, this difference in thepassing distances may be relatively small however for a large number ofoscillations, the particle advances on average towards the axis. Thisrepresents a particle drifting motion.

As described above, and depicted in 402 of FIG. 4, the cross-sectionaldrifting motion of particles is actuated by the acoustic excitation ofthe channel walls 104. An imposed axial pressure gradient, in thex-direction, leads to axial fluid flow. This axial flow drives particlesdownstream, along the longitudinal axis 105. Axial velocity profile isdescribed approximately by Poiseuille formula with maximal velocity Uvalid near the channel axis.

Reference is now made to FIG. 7, which is a schematic illustration oftrajectories of two particles in a capillary, such as 102 on which aquadrupole acoustic field is applied, according to some embodiments ofthe present invention. In FIG. 7, x and y are normalized by r₀. Thetrajectories in FIG. 7 are of 1 μm particles in the capillary 102.Particles are seeded at the inlet 108 of the channel, for example asshown at coordinates (x₀=0, y₀=0.15) and (x₀=0, y₀=0.05), with theinitial velocity coinciding with that of air. It is seen that allparticles approach steadily the longitudinal axis 105. This describesacoustic focusing. For specificity 10-fold focusing is considered whenparticle's ordinate falls ten times. The corresponding time t_(1/10) andthe distance x_(1/10) characterize focusing efficiency. It is seen thatfor the data depicted in FIG. 7, 10-fold focusing occurs in about oneradius distance.

Optionally, as outlined above, the device 100 is unpartitioned andtherefore does not have spatially periodic configuration. In suchembodiments, the device 100 may be used to deliver the particles atatmospheric pressure, at relatively high Reynolds numbers, as lossesconnected with particle mixing pertinent are avoided. The Reynoldsnumbers are high relative to the Reynolds numbers of focusing spatiallyperiodic aerodynamic lens arrays. As the Reynolds numbers are relativelyhigh, the particle transmission rate is respectively relatively high.

According to some embodiments of the present invention, the device 100is used to focus particles in an inlet of an on-line single-particleanalyzer, such as an aerosol mass spectrometer and/or any analyticalchemistry analyzer, such as atmospheric science, biological detection,pharmaceutical manufacturing, and/or engine research.

According to some embodiments of the present invention, the device 100is employed in combination with aerodynamic lens arrays. In suchembodiments, the device 100 is used as an acoustic lens channel of someor all of the stages of a lens array. In such a manner, the particlesconcentration on each stage is enhanced and consequently the size of theorifices may be decreased, reducing the pumping costs.

It is expected that during the life of a patent maturing from thisapplication many relevant devices and methods will be developed and thescope of the term a capillary, a pump, and a vibration source isintended to include all such new technologies a priori.

As used herein the term “about” refers to ±10.

The terms “comprises”, “comprising”, “includes”, “including”, “having”and their conjugates mean “including but not limited to”. This termencompasses the terms “consisting of” and “consisting essentially of”.

The phrase “consisting essentially of” means that the composition ormethod may include additional ingredients and/or steps, but only if theadditional ingredients and/or steps do not materially alter the basicand novel characteristics of the claimed composition or method.

As used herein, the singular form “a”, “an” and “the” include pluralreferences unless the context clearly dictates otherwise. For example,the term “a compound” or “at least one compound” may include a pluralityof compounds, including mixtures thereof.

The word “exemplary” is used herein to mean “serving as an example,instance or illustration”. Any embodiment described as “exemplary” isnot necessarily to be construed as preferred or advantageous over otherembodiments and/or to exclude the incorporation of features from otherembodiments.

The word “optionally” is used herein to mean “is provided in someembodiments and not provided in other embodiments”. Any particularembodiment of the invention may include a plurality of “optional”features unless such features conflict.

Throughout this application, various embodiments of this invention maybe presented in a range format. It should be understood that thedescription in range format is merely for convenience and brevity andshould not be construed as an inflexible limitation on the scope of theinvention. Accordingly, the description of a range should be consideredto have specifically disclosed all the possible subranges as well asindividual numerical values within that range. For example, descriptionof a range such as from 1 to 6 should be considered to have specificallydisclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numberswithin that range, for example, 1, 2, 3, 4, 5, and 6. This appliesregardless of the breadth of the range.

Whenever a numerical range is indicated herein, it is meant to includeany cited numeral (fractional or integral) within the indicated range.The phrases “ranging/ranges between” a first indicate number and asecond indicate number and “ranging/ranges from” a first indicate number“to” a second indicate number are used herein interchangeably and aremeant to include the first and second indicated numbers and all thefractional and integral numerals therebetween.

It is appreciated that certain features of the invention, which are, forclarity, described in the context of separate embodiments, may also beprovided in combination in a single embodiment. Conversely, variousfeatures of the invention, which are, for brevity, described in thecontext of a single embodiment, may also be provided separately or inany suitable subcombination or as suitable in any other describedembodiment of the invention. Certain features described in the contextof various embodiments are not to be considered essential features ofthose embodiments, unless the embodiment is inoperative without thoseelements.

Although the invention has been described in conjunction with specificembodiments thereof, it is evident that many alternatives, modificationsand variations will be apparent to those skilled in the art.Accordingly, it is intended to embrace all such alternatives,modifications and variations that fall within the spirit and broad scopeof the appended claims.

All publications, patents and patent applications mentioned in thisspecification are herein incorporated in their entirety by referenceinto the specification, to the same extent as if each individualpublication, patent or patent application was specifically andindividually indicated to be incorporated herein by reference. Inaddition, citation or identification of any reference in thisapplication shall not be construed as an admission that such referenceis available as prior art to the present invention. To the extent thatsection headings are used, they should not be construed as necessarilylimiting.

1. A method of focusing a plurality of discrete particles, comprising:establishing a flow of a fluid medium carrying a plurality of discreteparticles within a capillary having a plurality of separate walls and alongitudinal axis; and vibrating said plurality of separate walls toapply an acoustic field having a central axis substantially along saidlongitudinal axis, said acoustic field focusing said plurality ofdiscrete particles substantially along said longitudinal axis.
 2. Themethod of claim 1, wherein said plurality of separate walls areseparately vibrated in a frequency of less than 10 Mega Hertz (10 MHZ).3. The method of claim 1, wherein said acoustic field is a substantiallyquadrupole acoustic field.
 4. The method of claim 1, further comprisinganalyzing signals received from said particles, substantially along saidlongitudinal axis, to identify at least one characteristic of saidplurality of discrete particles.
 5. The method of claim 1, wherein saidacoustic field creates a plurality of streamlines each between twoadjacent walls of said plurality of separate walls, said applyingcomprises maneuvering said plurality of particles along saidstreamlines, toward said longitudinal axis.
 6. The method of claim 1,wherein said vibrating comprises maneuvering each said particle inoscillating motions toward said longitudinal axis.
 7. The method ofclaim 1, wherein said plurality of particles are plurality of discreteparticles.
 8. The method of claim 1, wherein said plurality of separatewalls form a substantially unpartitioned inner lumen.
 9. The method ofclaim 1, wherein said vibrating comprising vibrating plurality ofseparate walls are separately vibrated in a frequency of about 1 KiloHertz (1 KHz).
 10. A device of focusing a plurality of particles,comprising: a capillary having a longitudinal axis and a substantiallyunpartitioned lumen to flow a fluid medium having a plurality ofparticles; and at least one vibration source for vibrating saidcapillary in a frequency of less than 10 Mega Hertz (MHz) so as to focussaid plurality of particles along said longitudinal axis.
 11. The deviceof claim 10, wherein said inner lumen having a diameter of about 10millimeter.
 12. The device of claim 10, wherein said capillary having aplurality of separate walls and a plurality of slits, each said slitbeing formed between each adjacent pair of walls of said plurality ofseparate walls.
 13. The device of claim 12, wherein said plurality ofseparate walls are separated from one another.
 14. The device of claim12, wherein each said vibration source is connected to vibrate one ofsaid plurality of separate walls.
 15. The device of claim 12, whereineach separate wall is convex toward a longitudinal axis of saidcapillary.
 16. The device of claim 12, wherein each separate wall isconcave toward a longitudinal axis of said capillary.
 17. The device ofclaim 12, wherein said at least one vibration source comprises aplurality of vibration sources arranged to vibrate said capillary so asto form a quadrupole acoustic field having a central axis substantiallyalong a longitudinal axis of said capillary.
 18. The device of claim 10,wherein said capillary having four plurality of separate walls arrangedto form a cylindrical lumen.
 19. An aerodynamic lens array having thedevice of claim 10 as a lens in at least one stage.
 20. Asingle-particle analyzer having the device of claim 12 for focusing saidplurality of particles before an analysis thereof.
 21. A device offocusing a plurality of particles, comprising: a capillary having alongitudinal axis and a plurality of walls sized and shaped to flow afluid medium having a plurality of particles; and a plurality ofvibration sources each separately vibrates one of said plurality ofwalls so as to focus said plurality of particles along said longitudinalaxis.